Clinical trial phases

Clinical trials of investigational treatments are conducted in “phases” from early, small-scale Phase 1 trials to late-stage, large-scale Phase 3 trials, with each phase building on what was learned in the previous one. Each phase has a different purpose and is designed to help researchers answer specific questions. Sometimes, certain parts of two phases are carried out in parallel in so-called combined phase clinical trials.

Preclinical phase
Phase 1
Phase 2
Phase 3
Phase 4

Before an investigational medicine can enter clinical trials in humans, it goes through several laboratory studies to evaluate if it can proceed to human clinical trials.

A Phase 1 clinical trial assesses the safety and tolerability of an investigational medicine and how it may generally interact with the body (i.e. data on how the investigational medicine moves throughout our body, how it is broken down, and how long it stays in the body). This information also helps researchers to define the right dosage.

  • Often includes less than 100 participants
  • Participants are healthy volunteers or patients with a specific type of severe disease fulfilling predefined criteria

A Phase 2 clinical trial evaluates the safety and tolerability of the investigational medicine in a larger group of participants. It also evaluates signs for early efficacy of the investigational medicine.

  • Usually includes 100-300 participants
  • Participants have a specific condition fulfilling predefined criteria
  • Participants in a certain randomly assigned trial group may receive a placebo or the standard of care treatment instead of the investigational medicine as a comparator
  • Helps gather additional information on the right dosage

A Phase 3 clinical trial assesses the investigational medicine’s safety and efficacy in an even larger group of participants, often compared to the current standard of care, if one is available, to evaluate whether the investigational medicine might provide an additional benefit for patients. Phase 3 is the final step before the investigational medicine is submitted to a regulatory authority for market approval.

  • Usually includes 300-3,000 participants
  • Participants have a specific condition fulfilling predefined criteria

After receiving market approval, a medicine is available for use in routine clinical practice. Phase 4 trials are used for post-approval observation to continue to assess the safety and efficacy of a medicine along with long-term effects in a real-world setting.

  • Usually includes several thousand participants with a specific condition

Female scientist in standing in the laboratory

Combined phase clinical trials

In drug development, clinical trials can also start with a combined Phase 1 and Phase 2 clinical trial, referred to as Phase 1/2, if the investigational medicine and medical need meet certain criteria. This type of clinical trial simultaneously evaluates the safety and early signs of efficacy of the investigational medicine. Combined phase clinical trials - both Phase 1/2 and Phase 2/3 - may allow research questions to be answered more quickly and thus develop potential new treatments faster.

Doctor showing some data to a patient

Clinical trials safety

Before clinical trials can begin, they must undergo a specific approval process. Researchers, medical institutions, or pharmaceutical companies must define the trial’s exact objective and plan how it will be conducted. The defined design must then be approved by independent ethics committees to ensure the trial meets ethical standards, legal requirements and that participants are receiving the state-of-the-art of medical care. Additionally, government health authorities must approve the trial to ensure it meets national and international standards.

During the trial, participants are closely monitored – both to ensure their health and to ensure that the trial is conducted according to international ethical and scientific quality standards, called Good Clinical Practice.

Frequently asked questions

What is blinding?

The term “blinding” is used in a clinical trial to describe whether a trial participant and/or their physician are informed whether they are given the investigational treatment or, for example, a placebo. If the trial participant alone does not know, it is called a single-blind trial. If both, trial participant and physician, do not know, it is called double-blind trial. Blinding a clinical trial helps to prevent bias and expectations and to make the trial as accurate as possible.

What is a placebo?

 A placebo is a treatment that looks like a regular treatment but is made with inert ingredients, for example a sugar pill or saline injection, that have no effect on trial participant health. The physicians administering it will not know whether it is the actual investigational treatment or not. This helps the clinical research team to determine if the investigational treatment has a real effect on participants.

What is a healthy volunteer?

In clinical trials, healthy volunteers are people without significant health issues who participate in the clinical trials to evaluate the safety and tolerability of investigational drugs or vaccines. Healthy volunteers may also serve as a comparison group for patients with the disease under investigation. Both, healthy and patient volunteers, are crucial for clinical research.

What is an adverse event?

An adverse event is an untoward effect that might occur during treatment with an investigational drug, whether or not considered drug related. Adverse events may be mild, moderate, or severe. During a clinical trial, the research team closely monitors the participants to help them with any potentially occurring adverse events. However, it is important that the participants themselves also make the research team aware of any adverse events they might experience. To many people, adverse events and side effects mean the same thing and are used interchangeably, which is incorrect. Side effect is a subset of all adverse events meaning any adverse event where there is reason to conclude that the drug caused the event.

Are clinical trials safe?

Clinical trials undergo very strict regulations and policies to safeguard the privacy, health, safety, and well-being of trial participants. Before a clinical trial is allowed to start, it undergoes a specific multi-step approval process. During the clinical trial, the participants are closely monitored by the research team – both to ensure their health and the successful evaluation of the investigational medicine.

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